Are Electrocardiographic Criteria Reliable for Left Ventricular Hypertrophy Detection in Indian Adults?

Background: Left ventricular hypertrophy (LVH) detection is vital to the risk stratification of adults at risk of adverse cardiovascular events such as coronary heart disease, cerebrovascular disease, and aortic aneurysms. Electrocardiogram (ECG), a non-invasive, cost-effective instrument has been widely used as a screening tool for LVH. The objective of this study was to determine the diagnostic accuracy of seven frequently used ECG criteria in high-risk Indian adults in comparison with echocardiography. Methods: ECG and transthoracic echocardiography were performed in adults older than 18 years with at least one cardiac risk factor (chronic hypertension, obesity, ischemic heart disease, and type 2 diabetes mellitus). Precision and accuracy were calculated for the various ECG criteria against LVH based on left ventricular mass index (LVMI) and cardiac remodeling by echocardiography. Results: A total of 220 participants were enrolled. Of these, 96 had LVH by echocardiography. There was marked variability in LVH detection by the different ECG criteria: 28 by Sokolow-Lyon criteria, 26 by Cornell criteria, 24 by Lewis criteria, 46 by Scott criteria, eight by Romhilt-Estes criteria, six by Modified Cornell criteria, and only two by Roberts criteria. Agreement statistics between ECG criteria and LVMI showed that none of them had a good agreement for LVH detection. Conclusion: None of the ECG criteria were sensitive enough to rule out ventricular hypertrophy. In the context of cardiac remodeling, the ECG criteria had high sensitivity but low specificity and, hence, limited clinical relevance.


Introduction
Left ventricular hypertrophy (LVH), defined as an increase in left ventricular mass (LVM), is an indicator of left ventricular (LV) pressure or volume overload [1]. LVH is an integral component of cardiovascular risk stratification and is considered to be a surrogate marker of other cardiovascular risk factors integrated over time [2]. It may also contribute directly to cardiovascular disease through pathological changes in cardiac structure and function [3]. The presence of LVH is associated with a rapid increase in the risk of stroke, coronary heart disease, and heart failure. In the Framingham Heart Study, LVH has been associated with a three-fold increase in the incidence of cardiovascular events when compared with a normal heart [4]. Hence, the detection of LVH is integral to the risk stratification of adults at risk of adverse cardiovascular events and other related illnesses [5,6]. LVH can be identified by chest x-ray, electrocardiogram (ECG), echocardiogram, and cardiac MRI. The chest x-ray is neither sensitive nor specific for identifying LVH. Echocardiography has high sensitivity and specificity and is the modality of choice for diagnosing LVH [7]. However, echocardiography is not universally available in resource-poor settings, as it requires vast resources and trained personnel. ECG, a non-invasive, cost-effective instrument has been widely used as a screening tool for LVH. More than 30 criteria-based combinations of parameters of the 12-lead resting ECG have been used for decades to detect LVH [8]. Some of the widely used criteria are Lewis voltage, Gubner-Ungerleider voltage, Romhilt-Estes score, Sokolow-Lyon voltage criteria, Framingham criterion, Perugia criterion, etc. These voltage criteria were developed and validated in Caucasian populations; given the conspicuous racial differences in ECG characteristics, diagnostic accuracy in the Indian population is unproven [9].
The objective of this study was to determine the diagnostic accuracy of seven frequently used ECG criteria for LVH in high-risk Indian adults in comparison with the gold standard, i.e., echocardiography.

Materials And Methods
This prospective analytical study was conducted in a tertiary care hospital, Indira Gandhi Medical College & Research Institute, Puducherry, India. The project proposal for this study (12/158/IEC/PP/2018) was approved by Institute Ethics Committee (Human Studies), Indira Gandhi Medical College & Research Institute. Adults older than 18 years with at least one of the following risk factors, chronic hypertension, obesity, ischemic heart disease, and type 2 diabetes mellitus, were included in the study after informed consent. Patients with acute cardiac illness, rhythm disturbances, coexisting respiratory illness, and in whom a technically adequate LV study could not be performed were excluded from the study. Basic demographic parameters of age, sex, height, weight, abdominal circumference, blood pressure, comorbidities, and medications were entered in a predesigned proforma. Body surface area (BSA), using the Takahira formula, and BMI were calculated [10,11]. Standard 12-lead ECG with standardizations for each of the 12 leads was recorded at 25 mm/s and 10 mm/mV. For LVH detection, the following criteria-based Limb lead voltage (Lewis Score), Precordial lead voltage (Cornell, Modified Cornell, Sokolow-Lyon, and Roberts Criteria), Combination of the limb and precordial voltage (Scott criteria), Combination of voltage and nonvoltage (Romhilt-Estes point score) were applied (Appendix 1).
Transthoracic echocardiographic examination was performed by a physician who was blinded to the ECG findings and trained in echocardiography, using a Philips HD7XE echocardiogram machine (Koninklijke Philips N.V., Amsterdam, Netherlands). The LV was visualized with the patient lying in a modified left lateral decubitus position, with the probe at the left parasternal window angled to visualize the heart in the long axis view. All the M-mode and two-dimensional (2D) measurements were performed by the leading edge-toleading edge method, as described by the American Society of Echocardiography (ASE) [12]. Echocardiographic gender-specific grading of ventricular hypertrophy was performed based on the thickness of the interventricular septum, LV posterior wall thickness, and end-diastolic diameter values according to the recommendations of the ASE [13]. LVM was calculated according to the Devereux formula where LVEDd is LV diastolic diameter, IVSd is intraventricular septal diameter, and LVPWd is LV posterior wall diastolic thickness) [14].  Relative wall thickness (RWT) was calculated using the formula where LVPWd is posterior wall diastolic thickness and LVEDd is LV diastolic diameter. LVM index (LVMI), another indicator of LVH, was calculated as a ratio of LVM and BSA (Appendix 2).
Data were systematically recorded and analyzed using SPSS Statistics for Windows, Version 17.0 (Released 2008; SPSS Inc., Chicago, United States). Precision and accuracy were calculated for the various ECG criteria against LVH based on LVMI and cardiac remodeling subtypes. Kappa agreement was done to identify the most reliable ECG indicator for diagnosing LVH. Values > 0.75 are considered excellent ones, values < 0.40 as poor concordance, and those between 0.40 and 0.75 as good concordance. Statistical significance was verified in all comparisons by using 95% confidence intervals and a p-value < 0.05.

Results
A total of 220 participants were enrolled in the study; 91 (41.3%) were males and 129 (58.7%) were females. The majority of the subjects were between 40 and 69 years, and the mean age was 53.6 years ( Figure 2).

FIGURE 2: Age and gender-wise distribution of the study population
Of the patients, 27% were overweight, and 13.6% were obese based on BMI; 41 males had a waist circumference ≥ 90 cm, while 106 females had a waist circumference ≥ 80 cm. Systolic hypertension was present in 19.1%, while the prevalence of diastolic hypertension was 15.0%.           [8,15]. Nevertheless, clinicians have accepted ECG as an essential clinical instrument, despite its perceptible deficiencies.
The accuracy of ECG criteria depends on the prevalence and severity of LVH in the population in which they were developed. Unless tested and proven, the precision of these criteria in our population is questionable due to the inherent difference in the composition and prevalence of LVH. Many studies from high-resource settings have tried to improve the accuracy of ECG criteria for the diagnosis of LVH [16,17]. So far, to the best of our knowledge, very few studies have been conducted to evaluate the reliability and accuracy of various ECG criteria in our population. This research was performed to identify the ECG criterion among the commonly used limb and precordial lead-based voltage criteria, which will be the holy grail of LVH detection in high-risk patients from resource-poor settings.
In the Caucasian population, some studies found that Cornell and Cornell product (CP) criteria performed better than the Sokolow-Lyon index, whereas others delivered conflicting opinions [18]. In our study, none of the ECG criteria demonstrated sensitivity or specificity high enough for reliable detection of anatomically diagnosed LVH. The lack of sensitivity and specificity of widely used ECG criteria make them unacceptable for detecting the presence of echocardiographically confirmed ventricular hypertrophy and, hence, are unsuitable for clinical use in the Indian Adult population.
It is well known that cardiac remodeling is a key aspect of cardiovascular disease progression [19]. Abnormal ECG changes can precede pathological echocardiographic findings, and electrical alterations can add further information to the imaging of cardiac structure [20]. Hence, we studied the reliability and accuracy of the ECG criteria to detect the various types of cardiac remodeling. All the studied criteria demonstrated high sensitivity but low specificity. This shows that though ECG changes do occur in LVH, the commonly used ECG criteria are not clinically useful in detecting the types of cardiac remodeling.
Being a single-center study, the major limitation is the generalizability of the study pending similar research in a larger population. Also, the distribution of the study population was bell-shaped, and more subjects are needed in the extremes of age groups before the conclusions can be generalized.

Conclusions
Existing ECG criteria should be considered insensitive methods for detecting anatomic LVH in Indian Adults. With reference to cardiac remodeling, the criteria studied had high sensitivity but low specificity and hence, have limited clinical relevance. Therefore, we suggest that further research is required to develop ECG-based criteria for the detection of anatomical LVH in the Indian population. Delayed intrinsicoid deflection (interval between beginning of QRS interval and the peak of the R wave) in V5 or V6 (>0.05 sec) 1 A score of ≥ 5 indicates "definite" LVH; a score of 4 indicates "probable" LVH.